The bioactivity of circulating LH appears to be rapidly modulated by gonadal steroids (i.e. normal men have higher B:I than cycling females; castration in rats decrease the B:I). Also, the decrease in B:I of LH in castrated animals and differences in B:I observed in men vs cycling females could be related to increased LH secretion and/or production rate. Previous estimates of LH blood production derived from immunoassay data markedly underestimated the quantity of bioactive LH secreted in man. The estimated bioactive blood production rate is about 30 fold higher than for LH immunoactivity, values that are in accord with the plasma B:I ratio of 4 in normal men. Metabolic clearance rate for LH bioactivity was 33% less than that for immunoactivity. Results indicate that high endogenous production rates represent a predominant factor responsible for the high B:I ratio characteristic of plasma LH in normal men. As previously observed with testosterone pulsation in men it is unlikely that a temporal relationship exists between individual bioactive LH and pulses of progesterone secreted by the late corpus luteum. Opioids slow GnRH pulses at the hypothalamic level and cause inhibition of LH secretion. The opiate antagonist, nalterexone, increases pulse frequency and mean integrated bioactive LH. Dissection of an early releasable LH pool by a single dose of IV naloxone could be of value to complement the GnRH test in physiopathological exploration of hypothalamic function in man. Steroids can modify GnRH secretion and E2 replacement reinstates opioid suppression of bioactive LH secretion in orchidectomized patients with testicular feminization. Also, direct inhibitory effects of opioids on LH secretion, through high affinity pituitary receptors, could further modulate LH bioactivity. Using an in vitro lactogen bioassay, definite prolactin pulsations were detected at all stages of the cycle and B:I ratios were blow or near unity. In contrast, serum B:I were elevated during the rat proestrus surge. Prolactin biopeotency is much higher in the rat than in the human and increases at proestrous, reflecting the physiological relevance of this hormone to luteal function in this species.